Evidence for disturbed S-adenosylmethionine:S-adenosylhomocysteine ratio in patients with end-stage renal failure: A cause for disturbed methylation reactions?

Abstract

Background. Elevated homocysteine concentrations have been associated with premature arteriosclerosis and with impairment of key methylation reactions through accumulation of the homocysteine metabolite S-adenosylhomocysteine. In end-stage renal failure high homocysteine concentrations are commonly found but thus far the concentrations of related adenosylated metabolites in plasma have not been assessed. Methods. In this prospective study we determined plasma homocysteine and related metabolites in 25 patients on regular haemodialysis, and in 40 healthy volunteers. Blood samples from patients were drawn immediately before and in 10 patients additionally after the dialysis session. Results. Folic acid and vitamin B12 in plasma were similar in patients (mean ± SEM 25 ± 2 nmol/l and 400 ± 41 pmol/l respectively) and controls (24 ± 3 and 324 ± 23 respectively). In patients plasma homocysteine, S-adenosylmethionine and S-adenosylhomocysteine were markedly elevated (36.6 ± 3.6 μmol/l, 381 ± 32 nmol/l and 1074 ± 55 nmol/l respectively) compared to the control values (6.8 ± 0.4 μmol/l, 60 ± 3 nmol/l and 24.4 ± 1.1 nmol/l respectively) whereas the molar ratio of plasma S-adenosylmethionine and S-adenosylhomocysteine was significantly decreased (0.36 ± 0.02 and 2.7 ± 0.2 in patients and controls respectively). Haemodialysis failed to normalize the abnormal levels of these metabolites. Conclusion. Since the ratio of S-adenosylmethionine:S-adenosylhomocysteine is closely linked to the activity of numerous enzymatic methylation reactions, these results suggest that methylation may be impaired in these patients.